Hemophilus influenzae is a major cause of human disease, particularly in children less than two years of age. Failure of a capsular polysaccharide vaccine to protect the very young, plus the need to control disease caused by unencapsulated H. influenzae, prompted us to investigate the protein surface antigens (i.e., outer membrane proteins), their role in pathogenicity and the host immune response to them. We have since isolated outer membranes, characterized their protein composition in a variety of strains, shown the usefulness of these molecules for epidemiological studies, and demonstrated that healthy adults and convalescent infants, children and adults produce antibodies to the outer membrane proteins. We now propose to continue this research with the following objectives: to increase the power of outer membrane proteins as an epidemiological tool, to describe the physical and chemical properties of outer membrane proteins, and factors affecting their biosynthesis, to identify those outer membrane proteins that are on the surface of the cell and that are also immunogenic in humans, to ascertain if antibody to these surface immunogens is protective, to purify these proteins, and to measure the amount and class of antibody in sera from healthy adults and acutely ill and convalescent patients of all ages. These objectives will be reached by a combination of biochemical and immunological techniques: sodium dodecylsulfate polyacrylamide gel electrophoresis, counterimmuno-electrophoresis, gel filtration, ion exchange chromatography, ELISA and RIA methods, and model animal studies. The results will increase our general understanding of the pathogenicity of H. influenzae and should guide us in devising means of preventing both systemic (meningitis, epiglottits) and local (otitis media) disease.